The principal objective of the proposed research is to elucidate the role of protein phosphorylation in the process of synaptic transmission in the peripheral nervous system. For the purpose of this study, the mammalian superior cervical ganglion will be used as a model containing nerve cell bodies and synapses. The effect of physiological activity and of various pharmacological manipulations will be studied on the state of phosphorylation of Protein I and of other phosphoproteins in this preparation. (Protein I is a phosphoprotein localized exclusively in the synaptic vesicle and synaptic membrane regions of nerve cells.) We will attempt to determine these phosphorylated proteins are located presynaptically or postsynaptically, whether their phosphorylation is associated with regulation of neurotransmitter release or neurotransmitter action, and whether alterations in the state of phosphorylation of these proteins are mediated via cyclic AMP-dependent protein kinase, cyclic GMP-dependent protein kinase, or calcium-dependent protein kinase. In order to study the role of protein phosphorylation in the physiology of the presynaptic nerve terminal, we shall also use the guinea pig ductus deferens. In this preparation, too, we shall study the effect of physiological activity and of various pharmacological manipulations on the state of phosphorylation of Protein I and other phosphoproteins which serve as substrates for cyclic AMP-dependent, cyclic GMP-dependent, and calcium-dependent protein kinases.